Inhibition of GABA metabolism in rat brain slices by halothane.
Based on studies with rat cerebral cortex slices, it was previously hypothesized that halothane anesthesia may result from increased GABA (gamma-aminobutyric acid) content in the synapses. Since GABA is an inhibitory neurotransmitter, such increases may cause a reduction in synaptic activity. The increase in GABA content could arise from several possible causes which are examined in this study using rat cerebral cortex slices as a model. The effects of halothane on uptake, release, and catabolism of GABA were determined. Uptake was studied by the amounts of radioactive GABA accumulated by the slices, and release studied by that discharged into the medium from slices preloaded with radioactive GABA. Catabolism was assessed by preloading the slices with radioactive GABA and then followed by measuring the amount of radioactivity found in unmetabolized GABA or in pooled GABA metabolites. Since CO2 was established as a major metabolite, it was subsequently used alone to measure the inhibition of GABA catabolism in the presence of  varying amounts of halothane. Halothane (3 per cent) did not affect the high-affinity uptake or the release of GABA but did inhibit the catabolism of GABA. Using 14CO2 production as an index of catabolism, the inhibition of GABA catabolism by halothane was dose-related (8.79 per cent inhibition/per cent halothane). Such results support the hypothesis that halothane anesthesia may result at least in part from an inhibition of GABA catabolism which, in turn, causes increased GABA level in the synapse with resultant synaptic inhibition.
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013569:Synapses / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D002245:Carbon Dioxide; D005680:gamma-Aminobutyric Acid; D006221:Halothane